Pin1 links the activities of c-Abl and p300 in regulating p73 function

Fiamma Mantovani, Silvano Piazza, Monica Gostissa, Sabrina Strano, Paola Zacchi, Roberto Mantovani, Giovanni Blandino, Giannino Del Sal

Research output: Contribution to journalArticle

Abstract

Activation of p73 upon genotoxic treatment triggers apoptosis of tumor cells lacking functional p53 and involves the activities of c-Abl and p300. Here, we demonstrate that conformational changes of p73 catalyzed by the prolyl isomerase Pin1 are crucial in this pathway. Lack of Pin1 reduces p73 stability, hampering its accumulation upon genotoxic stress. Indeed, we show that upon treatment with chemotherapeutic drugs c-Abl enhances the phosphorylation- dependent interaction between Pin1 and p73, and this in turn promotes p73 acetylation by p300. Consistently, the ability of c-Abl and p300 to increase p73 stability and transcriptional activity requires Pin1. As a consequence, Pin1 appears to be essential for activation of the apoptotic response by endogenous p73.

Original languageEnglish
Pages (from-to)625-636
Number of pages12
JournalMolecular Cell
Volume14
Issue number5
DOIs
Publication statusPublished - Jun 4 2004

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Peptidylprolyl Isomerase
Acetylation
DNA Damage
Phosphorylation
Apoptosis
Pharmaceutical Preparations
Neoplasms

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Mantovani, F., Piazza, S., Gostissa, M., Strano, S., Zacchi, P., Mantovani, R., ... Del Sal, G. (2004). Pin1 links the activities of c-Abl and p300 in regulating p73 function. Molecular Cell, 14(5), 625-636. https://doi.org/10.1016/j.molcel.2004.05.007

Pin1 links the activities of c-Abl and p300 in regulating p73 function. / Mantovani, Fiamma; Piazza, Silvano; Gostissa, Monica; Strano, Sabrina; Zacchi, Paola; Mantovani, Roberto; Blandino, Giovanni; Del Sal, Giannino.

In: Molecular Cell, Vol. 14, No. 5, 04.06.2004, p. 625-636.

Research output: Contribution to journalArticle

Mantovani, F, Piazza, S, Gostissa, M, Strano, S, Zacchi, P, Mantovani, R, Blandino, G & Del Sal, G 2004, 'Pin1 links the activities of c-Abl and p300 in regulating p73 function', Molecular Cell, vol. 14, no. 5, pp. 625-636. https://doi.org/10.1016/j.molcel.2004.05.007
Mantovani F, Piazza S, Gostissa M, Strano S, Zacchi P, Mantovani R et al. Pin1 links the activities of c-Abl and p300 in regulating p73 function. Molecular Cell. 2004 Jun 4;14(5):625-636. https://doi.org/10.1016/j.molcel.2004.05.007
Mantovani, Fiamma ; Piazza, Silvano ; Gostissa, Monica ; Strano, Sabrina ; Zacchi, Paola ; Mantovani, Roberto ; Blandino, Giovanni ; Del Sal, Giannino. / Pin1 links the activities of c-Abl and p300 in regulating p73 function. In: Molecular Cell. 2004 ; Vol. 14, No. 5. pp. 625-636.
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